title: Discriminating between latent and active tuberculosis with multiple biomarker responses.
abstract: We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), latent tuberculosis (N = 32), or no evidence of tuberculosis infection (N = 26) were evaluated. We used the Luminex Multiplexed Bead Array platform to simultaneously evaluate 25 biomarkers in the supernatant of whole blood samples following overnight stimulation using the Quantiferon(®) Gold In-Tube kit. We defined the response to stimulation as the difference (within an individual patient) between the response to the pooled tuberculosis antigens and the negative control. IP-10 response was significantly higher in tuberculosis-infected (active or latent) subjects compared to the uninfected group (p < 0.0001). Among the 25 parameters, expression levels of IL-15 and MCP-1 were found to be significantly higher in the active tuberculosis group compared to the latent tuberculosis group (p = 0.0006 and 0.0030, respectively). When combined, IL-15 and MCP-1 accurately identified 83% of active and 88% of latent infections. The combination of IL-15 and MCP-1 responses was accurate in distinguishing persons with active tuberculosis from persons with latent tuberculosis in this study.
authors.affiliation: Center for AIDS Research, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Frahm
authors.forename: Neela D
authors.initials: ND
authors.lastname: Goswami
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.forename: Emily
authors.initials: E
authors.lastname: Hecker
authors.forename: Ann
authors.initials: A
authors.lastname: Mosher
authors.forename: Emily
authors.initials: E
authors.lastname: Cadogan
authors.forename: Payam
authors.initials: P
authors.lastname: Nahid
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Jason E
authors.initials: JE
authors.lastname: Stout
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000097:blood* / Q000276:immunology; D055985:Latent Tuberculosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000097:blood / Q000276:immunology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019409:Interleukin-15